Neutralizing Antibodies Against the SARS-CoV-2 Omicron Variant (BA.1) 1 to 18 Weeks After the Second and Third Doses of the BNT162b2 mRNA Vaccine

Lassaunière, Ria; Polacek, Charlotta; Frische, Anders; Boding, Lasse; Sækmose, Susanne Gjørup; Rasmussen, Morten; Fomsgaard, Anders

doi:10.1001/jamanetworkopen.2022.12073

Cited by 44 publications

(53 citation statements)

References 6 publications

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“…However, neutralising antibodies against BA.1 and BA.2 significantly declined at month 3 post-booster vaccination, particularly in those without breakthrough infection, while neutralising antibodies to ancestral strain and Delta variant remained at high titers. We found no association between age and neutralising antibody levels, in line with a recent report [12], but none of our study participants were older than 57 years. Our findings are consistent with existing data regarding the capacity of the Omicron variant to escape from neutralizing antibodies induced by vaccination [10, 20].…”

Section: Discussionsupporting

confidence: 93%

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Kinetics of neutralising antibodies against Omicron variant in Vietnamese healthcare workers after primary immunisation with ChAdOx1-S and booster with BNT162b2

Châu

Nguyet

Dung

et al. 2022

Preprint

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We studied the development and persistence of neutralising antibodies against SARS-CoV-2 ancestral strain, and Delta and Omicron (BA.1 and BA.2) variants in Vietnamese healthcare workers (HCWs) up to 15 weeks after booster vaccination. We included 47 HCWs with different pre-existing immune statuses (group 1 (G1): n=21, and group 2 (G2): n=26 without and with prior breakthrough Delta variant infection, respectively). The study participants had completed primary immunisation with ChAdOx1-S and booster vaccination with BNT162b2. Neutralising antibodies were measured using a surrogate virus neutralisation assay. Of the 21 study participants in G1, neutralising antibodies against ancestral strain, Delta variant, BA.1 and BA.2 were (almost) abolished at month 8 after the second dose, but all had detectable neutralising antibodies to the study viruses at week two post booster dose. Of the 26 study participants in G2, neutralising antibody levels to BA.1 and BA.2 were significantly higher than those to the corresponding viruses measured at week 2 post breakthrough infection and before the booster dose. At week 15 post booster vaccination, neutralising antibodies to BA.1 and BA.2 dropped significantly, with more profound changes observed in those without breakthrough Delta variant infection. Booster vaccination enhanced neutralising activities against ancestral strain and Delta variant, as compared to those induced by primary vaccination. These responses were maintained at high levels for at least 15 weeks. Our findings emphasise the importance of the first booster dose in producing cross-neutralising antibodies against Omicron variant. A second booster dose might be needed to maintain long-term protection against Omicron variant.

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Section: Discussionsupporting

confidence: 93%

“…breakthrough and non-breakthrough infection. Yet, most of the reported data have been from high income countries [8][9][10][11][12][13][14], and few studies, especially those focusing on long term immunity, have been conducted in low-and middle-income countries.…”

Section: Introductionmentioning

confidence: 99%

Kinetics of neutralising antibodies against Omicron variant in Vietnamese healthcare workers after primary immunisation with ChAdOx1-S and booster with BNT162b2

Châu

Nguyet

Dung

et al. 2022

Preprint

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“…Thus, the reduced level of nucleocapsid detection is likely a result of slower replication and not lower production of the nucleocapsid protein [ 36 ]. We optimized and evaluated the neutralization assay prior to the emergence of the Omicron variant of concern, although the assay is appropriate for this variant as well [ 37 ]. Due to the slower endocytic entry pathway used by the Omicron variant, the virus should be titrated at 120 hours and during the neutralization assay, the incubation period adjusted to between 28 and 32 hours to allow for sufficient nucleocapsid protein production.…”

Section: Discussionmentioning

confidence: 99%

Optimization and evaluation of a live virus SARS-CoV-2 neutralization assay

et al. 2022

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Virus neutralization assays provide a means to quantitate functional antibody responses that block virus infection. These assays are instrumental in defining vaccine and therapeutic antibody potency, immune evasion by viral variants, and post-infection immunity. Here we describe the development, optimization and evaluation of a live virus microneutralization assay specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this assay, SARS-CoV-2 clinical isolates are pre-incubated with serial diluted antibody and added to Vero E6 cells. Replicating virus is quantitated by enzyme-linked immunosorbent assay (ELISA) targeting the SARS-CoV-2 nucleocapsid protein and the standardized 50% virus inhibition titer calculated. We evaluated critical test parameters that include virus titration, assay linearity, number of cells, viral dose, incubation period post-inoculation, and normalization methods. Virus titration at 96 hours was determined optimal to account for different growth kinetics of clinical isolates. Nucleocapsid protein levels directly correlated with virus inoculum, with the strongest correlation at 24 hours post-inoculation. Variance was minimized by infecting a cell monolayer, rather than a cell suspension. Neutralization titers modestly decreased with increasing numbers of Vero E6 cells and virus amount. Application of two different normalization models effectively reduced the intermediate precision coefficient of variance to <16.5%. The SARS-CoV-2 microneutralization assay described and evaluated here is based on the influenza virus microneutralization assay described by WHO, and are proposed as a standard assay for comparing neutralization investigations.

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“…The rapid and worldwide outbreak of SARS-CoV-2 has led to the emergence of various mutant strains, including Omicron and its subtypes. These variants have mutations in the RBD and have acquired higher binding affinity to ACE2 and evasion ability from neutralizing antibodies [ 50 , 51 , 52 ]. It is essential to rapidly prepare functional RBD to characterize the sequential emergence of mutant strains.…”

Section: Discussionmentioning

confidence: 99%

Characterization and Utilization of Disulfide-Bonded SARS-CoV-2 Receptor Binding Domain of Spike Protein Synthesized by Wheat Germ Cell-Free Production System

Yamaoka

Jeremiah

Funabashi

et al. 2022

Viruses

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The spike protein (SP) of SARS-CoV-2 is an important target for COVID-19 therapeutics and vaccines as it binds to the ACE2 receptor and enables viral infection. Rapid production and functional characterization of properly folded SP is of the utmost importance for studying the immunogenicity and receptor-binding activity of this protein considering the emergence of highly infectious viral variants. In this study, we attempted to express the receptor-binding region (RBD) of SARS-CoV-2 SP containing disulfide bonds using the wheat germ cell-free protein synthesis system. By adding protein disulfide isomerase (PDI) and endoplasmic reticulum oxidase (ERO1α) to the translational reaction mixture, we succeeded in synthesizing a functionally intact RBD protein that can interact with ACE2. Using this RBD protein, we have developed a high-throughput AlphaScreen assay to evaluate the RBD–ACE2 interaction, which can be applied for drug screening and mutation analysis. Thus, our method sheds new light on the structural and functional properties of SARS-CoV-2 SP and has the potential to contribute to the development of new COVID-19 therapeutics.

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Neutralizing Antibodies Against the SARS-CoV-2 Omicron Variant (BA.1) 1 to 18 Weeks After the Second and Third Doses of the BNT162b2 mRNA Vaccine

Cited by 44 publications

References 6 publications

Kinetics of neutralising antibodies against Omicron variant in Vietnamese healthcare workers after primary immunisation with ChAdOx1-S and booster with BNT162b2

Kinetics of neutralising antibodies against Omicron variant in Vietnamese healthcare workers after primary immunisation with ChAdOx1-S and booster with BNT162b2

Optimization and evaluation of a live virus SARS-CoV-2 neutralization assay

Characterization and Utilization of Disulfide-Bonded SARS-CoV-2 Receptor Binding Domain of Spike Protein Synthesized by Wheat Germ Cell-Free Production System

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